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Systemic Therapy for RAI-Refractory DTC

Panelists:Marcia S. Brose, MD, PhD, University of Pennsylvania; Naifa Busaidy, MD, FACP, FACE, University of Texas MD Anderson Cancer Center; Eric J. Sherman, MD, Memorial Sloan Kettering Cancer Center; R. Michael tuttle, MD, Memorial Sloan Kettering Cancer Center; Francis Paul Worden, MD, University of Michigan Comprehensive Cancer Center
Published: Monday, May 16, 2016


Transcript:

R. Michael Tuttle, MD:
Frank, you mentioned to send them back for RAI treatment. They usually start with us. We don’t get a lot back from you guys. Where should we, as practicing endocrinologists who have taken care of this, where do you want to get involved in these patients? Not the rapidly ones from the beginning, the ones that are growing more slowly over time. Where do you want to become part of the team or part of the process?

Frank Worden, MD: Right. I said send them back. It’s interesting, I live in Michigan, and so our catchment area is like the entire state of Michigan. And so one of my colleagues, your colleagues, Megan Haymart, published this very brilliant paper in JAMA saying that people get RAI kind of depending on where they live.

R. Michael Tuttle, MD: Yes, without a doubt.

Frank Worden, MD: And what doses they get. It’s very fascinating. So, people will come to us, and soon it’s very confusing. That’s why I said, well, I’ll send you back because I definitely want your opinion regarding those middle ground cases, such as Marcia is describing. But what’s interesting, I prefer—and I think Marcia, Eric probably does as well—to see them when they become refractory earlier rather than later. What I find sometimes is the outside-of-Michigan endocrinologist will hang on to the patients a little longer, managing their TSH which they’re suppressing, which is great. By the time they come to me, they’ve already developed those symptoms, that shortness of breath or that extensive bone pain that should have been irradiated. Now their pelvis is half eaten or whatnot. Those people should be seen earlier. So, I, personally, am on a big movement to have these patients seen earlier when we really are kind of on that cusp of saying they’re refractory to iodine or we know they’re refractory.

Marcia S. Brose, MD, PhD: Yes. And even the asymptomatic patients, there are a lot of things we do before patients go on kinase inhibitors, that we can help them have a better outcome if we can get them to a gym and start doing weightlifting and all of these things. And people laugh and they’re like you really do that? And I’m like, 80 year-old ladies I’m sending to the gym.

Frank Worden, MD: That’s what we do, too.

Marcia S. Brose, MD, PhD: And it makes a huge difference, but there’s a lot of education that we can be doing during that period, what we would call active surveillance, where we’re still deciding when they’re going to need it. We can do a lot of interventions and a lot of education. So I agree, the sooner I get them, the better. I don’t have to see them that often, but I want to at least have my eyes on them at least once or twice a year before then.

R. Michael Tuttle, MD: Talk about that, Eric, because we share a lot of patients together and we tend to cross over for a year or two. And it seems like at first you see them less frequently, I see them more frequently, and then that begins to shift as they begin. Talk about how you like to do that transition between our clinic and your clinic.

Eric Sherman, MD: You definitely did not want to see the person just when they’re ready to start treatment or worse, when I first started out, about 2 weeks before they went on hospice. Even for clinical trials, we want to get them ready for it, and we want to know, what are the mutations that are driving their tumor? Because we know those are the patients—like the early ones—that those mutations may play a role in investigational treatment. And even how often we watch them. There are certain things I think that the endocrinologist will do without thinking, just even giving contrast to a scan, something simple like that. It’s almost ingrained with endocrinologists, ‘I’m not going to give contrast to something, and redo that. No contrast.’ There’s a lot of things that we want to watch out for early so we know when they’re right to start treatment. We’ve already got a relationship set up with them, they know us, they know what the options that are going to exist are at that time, and we’ve done the scans and everything at the rate that we think is appropriate for them. But a lot of the patients will begin. I’ll do a scan every 6 months or every year. I won’t see them every 3 months, but it’s nice to know that ahead of time than at the point where the person is saying, ‘I’m seeing Dr. Sherman, I’m dead.’

Marcia S. Brose, MD, PhD: Yes, and that psychologically is very important. They don’t want to be thinking, “Oh, now I’m seeing Dr. Sherman, my days are numbered.” You really want that transition to be so that he’ll like Dr. Sherman as much as he liked you.

R. Michael Tuttle, MD: Naifa, you went through this transition. Trained as a very classic endocrinologist at MD Anderson, and you guys really think about thyroid cancer a lot like oncologists now. You’re using some of the TKIs yourself. Talk a little bit about that transition, about how you had to think about thyroid cancer differently as an endocrinologist to begin thinking about some of the issues these guys are thinking about.

Naifa Busaidy, MD, FACP, FACE: So, when you’re trained as an endocrinologist, you’re used to treating chronic diseases. But when it comes to thyroid cancer, you’ve always been trained that, okay, you have your surgery, you have your radioactive iodine, you have your surgery, you have your radioactive iodine, and done. And, as we cross trained with a lot of our colleague oncologists, you have to think about a lot of other things in terms of what are your goals. Is it improving overall survival? Is it trying to decrease the recurrences that you have to go through? Then thinking about what are the adverse events, or the side effects from the treatments, that are available or that are out there. And how does this patient’s lifestyle and comorbidities going to interplay with the drugs? So, you have to think about a lot of different angles that you didn’t necessarily think about when all you had was surgery and radioactive iodine.

We’re always thinking about the whole patient, but when it comes to systemic therapy, we’ve got to figure out if this is the long-term living patient with the distant metastatic disease that’s just hanging out there and living a great life and asymptomatic. Or is it the patient whose disease is rapidly progressing? But I agree with what Frank, Marcia, and Eric have all said. I think that whenever you, as an endocrinologist, are going to treat and think like an oncologist—and treat with these tyrosine kinase inhibitors, or other systemic therapies, or you’re going to introduce them to the oncologist—I think getting the oncologist or those thought processes in early is very important. Because that patient is very different from the head and neck cancer patient that comes in knowing, ‘Okay, if I don’t do something today, I’m going to die.’ This patient is like, ‘I’ve been sitting around with this disease for 15 years and now you’re sending me over to someone else who’s going to give me a systemic therapy. That means I’m dead.’ But they need that year or two to read about it, think about clinical trials, think about what their goals are. ‘Okay, I’m not going to be cured of this. Let me get my head wrapped around that.’ So, I think those discussions are very important for us, so, we happen to be the endocrinologist that also treats the oncologic aspect of it, but we go through the same thought processes that we needed to.

Frank Worden, MD: In addition to what you were saying about the clinical trials, I am all over clinical trials like I think most of you are here, too. The RIFTOS study is looking at how patients are progressing and when we start treatment with scans. I think that data are going to be really important to have. I think the more we see those, someone seeing them regularly should reassure them, and following them in that manner with studies such as this will be very helpful.

Marcia S. Brose, MD, PhD: And the last thing also is that you take your data—or Dr. Schlumberger’s data—that says once they are RAI refractory and their disease is growing—progressive disease—their overall survival is on average two-and-a-half to three-and-a-half years if you’re taking out the people who could have surgery. It’s really important I think for the community endocrinologist, as well as the oncologist, to understand that is a completely different patient. That patient is more like a lung cancer patient than they are like the bulk of the thyroid cancer patients. And, where I think we have still a challenge in our country, and maybe even around the world, is when an endocrinologist sees 95% of their patients are the good patients, to really teach them that this patient deserves to have early intervention and consideration because they will not be acting like those other ones. It’s hard sometimes to get them to take that rose colored glasses off.

R. Michael Tuttle, MD: It’s a perfect segue, Frank.

Transcript Edited for Clarity
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Transcript:

R. Michael Tuttle, MD:
Frank, you mentioned to send them back for RAI treatment. They usually start with us. We don’t get a lot back from you guys. Where should we, as practicing endocrinologists who have taken care of this, where do you want to get involved in these patients? Not the rapidly ones from the beginning, the ones that are growing more slowly over time. Where do you want to become part of the team or part of the process?

Frank Worden, MD: Right. I said send them back. It’s interesting, I live in Michigan, and so our catchment area is like the entire state of Michigan. And so one of my colleagues, your colleagues, Megan Haymart, published this very brilliant paper in JAMA saying that people get RAI kind of depending on where they live.

R. Michael Tuttle, MD: Yes, without a doubt.

Frank Worden, MD: And what doses they get. It’s very fascinating. So, people will come to us, and soon it’s very confusing. That’s why I said, well, I’ll send you back because I definitely want your opinion regarding those middle ground cases, such as Marcia is describing. But what’s interesting, I prefer—and I think Marcia, Eric probably does as well—to see them when they become refractory earlier rather than later. What I find sometimes is the outside-of-Michigan endocrinologist will hang on to the patients a little longer, managing their TSH which they’re suppressing, which is great. By the time they come to me, they’ve already developed those symptoms, that shortness of breath or that extensive bone pain that should have been irradiated. Now their pelvis is half eaten or whatnot. Those people should be seen earlier. So, I, personally, am on a big movement to have these patients seen earlier when we really are kind of on that cusp of saying they’re refractory to iodine or we know they’re refractory.

Marcia S. Brose, MD, PhD: Yes. And even the asymptomatic patients, there are a lot of things we do before patients go on kinase inhibitors, that we can help them have a better outcome if we can get them to a gym and start doing weightlifting and all of these things. And people laugh and they’re like you really do that? And I’m like, 80 year-old ladies I’m sending to the gym.

Frank Worden, MD: That’s what we do, too.

Marcia S. Brose, MD, PhD: And it makes a huge difference, but there’s a lot of education that we can be doing during that period, what we would call active surveillance, where we’re still deciding when they’re going to need it. We can do a lot of interventions and a lot of education. So I agree, the sooner I get them, the better. I don’t have to see them that often, but I want to at least have my eyes on them at least once or twice a year before then.

R. Michael Tuttle, MD: Talk about that, Eric, because we share a lot of patients together and we tend to cross over for a year or two. And it seems like at first you see them less frequently, I see them more frequently, and then that begins to shift as they begin. Talk about how you like to do that transition between our clinic and your clinic.

Eric Sherman, MD: You definitely did not want to see the person just when they’re ready to start treatment or worse, when I first started out, about 2 weeks before they went on hospice. Even for clinical trials, we want to get them ready for it, and we want to know, what are the mutations that are driving their tumor? Because we know those are the patients—like the early ones—that those mutations may play a role in investigational treatment. And even how often we watch them. There are certain things I think that the endocrinologist will do without thinking, just even giving contrast to a scan, something simple like that. It’s almost ingrained with endocrinologists, ‘I’m not going to give contrast to something, and redo that. No contrast.’ There’s a lot of things that we want to watch out for early so we know when they’re right to start treatment. We’ve already got a relationship set up with them, they know us, they know what the options that are going to exist are at that time, and we’ve done the scans and everything at the rate that we think is appropriate for them. But a lot of the patients will begin. I’ll do a scan every 6 months or every year. I won’t see them every 3 months, but it’s nice to know that ahead of time than at the point where the person is saying, ‘I’m seeing Dr. Sherman, I’m dead.’

Marcia S. Brose, MD, PhD: Yes, and that psychologically is very important. They don’t want to be thinking, “Oh, now I’m seeing Dr. Sherman, my days are numbered.” You really want that transition to be so that he’ll like Dr. Sherman as much as he liked you.

R. Michael Tuttle, MD: Naifa, you went through this transition. Trained as a very classic endocrinologist at MD Anderson, and you guys really think about thyroid cancer a lot like oncologists now. You’re using some of the TKIs yourself. Talk a little bit about that transition, about how you had to think about thyroid cancer differently as an endocrinologist to begin thinking about some of the issues these guys are thinking about.

Naifa Busaidy, MD, FACP, FACE: So, when you’re trained as an endocrinologist, you’re used to treating chronic diseases. But when it comes to thyroid cancer, you’ve always been trained that, okay, you have your surgery, you have your radioactive iodine, you have your surgery, you have your radioactive iodine, and done. And, as we cross trained with a lot of our colleague oncologists, you have to think about a lot of other things in terms of what are your goals. Is it improving overall survival? Is it trying to decrease the recurrences that you have to go through? Then thinking about what are the adverse events, or the side effects from the treatments, that are available or that are out there. And how does this patient’s lifestyle and comorbidities going to interplay with the drugs? So, you have to think about a lot of different angles that you didn’t necessarily think about when all you had was surgery and radioactive iodine.

We’re always thinking about the whole patient, but when it comes to systemic therapy, we’ve got to figure out if this is the long-term living patient with the distant metastatic disease that’s just hanging out there and living a great life and asymptomatic. Or is it the patient whose disease is rapidly progressing? But I agree with what Frank, Marcia, and Eric have all said. I think that whenever you, as an endocrinologist, are going to treat and think like an oncologist—and treat with these tyrosine kinase inhibitors, or other systemic therapies, or you’re going to introduce them to the oncologist—I think getting the oncologist or those thought processes in early is very important. Because that patient is very different from the head and neck cancer patient that comes in knowing, ‘Okay, if I don’t do something today, I’m going to die.’ This patient is like, ‘I’ve been sitting around with this disease for 15 years and now you’re sending me over to someone else who’s going to give me a systemic therapy. That means I’m dead.’ But they need that year or two to read about it, think about clinical trials, think about what their goals are. ‘Okay, I’m not going to be cured of this. Let me get my head wrapped around that.’ So, I think those discussions are very important for us, so, we happen to be the endocrinologist that also treats the oncologic aspect of it, but we go through the same thought processes that we needed to.

Frank Worden, MD: In addition to what you were saying about the clinical trials, I am all over clinical trials like I think most of you are here, too. The RIFTOS study is looking at how patients are progressing and when we start treatment with scans. I think that data are going to be really important to have. I think the more we see those, someone seeing them regularly should reassure them, and following them in that manner with studies such as this will be very helpful.

Marcia S. Brose, MD, PhD: And the last thing also is that you take your data—or Dr. Schlumberger’s data—that says once they are RAI refractory and their disease is growing—progressive disease—their overall survival is on average two-and-a-half to three-and-a-half years if you’re taking out the people who could have surgery. It’s really important I think for the community endocrinologist, as well as the oncologist, to understand that is a completely different patient. That patient is more like a lung cancer patient than they are like the bulk of the thyroid cancer patients. And, where I think we have still a challenge in our country, and maybe even around the world, is when an endocrinologist sees 95% of their patients are the good patients, to really teach them that this patient deserves to have early intervention and consideration because they will not be acting like those other ones. It’s hard sometimes to get them to take that rose colored glasses off.

R. Michael Tuttle, MD: It’s a perfect segue, Frank.

Transcript Edited for Clarity
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